Identification of genes in fruit flies
may shed light on cancer spread

By Audrey Huang
Johns Hopkins Medicine

By searching through all the genes
in the fruit fly genome, Johns Hopkins
scientists have identified those
required for a certain type of cell migration
and simultaneously captured a global view
of all the genes turned on when cells are on
the move.

The study, published April 3 in Developmental
Cell, has implications for understanding
cell migration and perhaps controlling
cancer cells that move similarly to spread
beyond an original tumor, the eventual
cause of death for most cancer patients.

The research identified several hundred
genes that are preferentially turned on in socalled
border cells of the fruit fly ovary that
migrate during normal development. Two
main types of genes came out of this search:
those known to be involved in maintaining
cell shape and structure and which become
very dynamic in migrating cells, and a group
of genes involved in transporting materials
from the inside of a cell to its membrane
surface and back again.

"So-called border cell migration shares
common characteristics with metastatic cancer
cells," said Xuejiao Wang, the first author
of the study and a postdoctoral fellow in the
School of Medicine's Department of Biological
Chemistry. "Cells must detach from where
they are, migrate between other cells and tissues,
and travel to a final destination."

Although border cell migration in the
fruit fly ovary may seem a far stretch for
studying human cancer metastasis, the genes
uncovered in this study share more similarities
with those that arise from studies
of human metastatic breast cancer cells
than they do with studies of other tissues in
the fruit fly, according to the study's senior
author, Denise Montell, a professor in Biological
Chemistry.

The 353 genes identified in this study
include some that are known to play a role
in both border cell migration in fruit flies
and in metastasis in animal cancer cells,
some that had long been suspected to play
a role in cell migration but have been more
difficult to study because their functions are
shared by other genes and some that are well
understood for their roles in other cellular
functions but without this study would not
have been obvious candidate genes in cell
migration. The results help these researchers
and others in the field by pointing out genes
to study further.

"This really was a hypothesis-generating
experiment," Montell said. "The results
of this study tell us where to focus future
efforts."

Understanding the genetic mechanisms
underlying cell migration is critical for understanding
normal development, and inflammation,
as well as metastasis. Classical genetic
approaches for identifying key genes—mutational
analysis, for example—have been successful
but generally yield information about
genes with unique functions only, and only
one gene at a time. Whole genome studies,
like the microarray analysis used in this
study, allow researchers to identify genes that
share similar functions in a way that mutational
analysis cannot. And, whole genome
approaches can look at most of the genes in
the genome at one time.

As part of their previous work, Montell's
group had generated mutant flies that show
defects in border cell migration. This study
identified five of the genes mutated in those
flies and gives the researchers a starting
point for more detailed analysis of how those
genes are involved in cell migration. Wang
has begun to study some of these genes to
further dissect their function. The researchers
also hope to perform more whole genome
analyses to identify genes that interact with
those already known to play a role in cell
migration and metastasis.

The researchers were funded by the Cell
Migration Consortium.

Authors on the paper are Wang, Jinyan
Bo, Tina Bridges and Montell, all of Johns
Hopkins; and Katherine Dugan, Tien-chi
Pan and Lewis Chodosh, of the Abramson
Family Cancer Research Institute at the
University of Pennsylvania School of Medicine.